Esterberg Robert, Fritz Andreas
Department of Biology, Emory University, Atlanta, GA 30322, USA.
Dev Biol. 2009 Jan 1;325(1):189-99. doi: 10.1016/j.ydbio.2008.10.017. Epub 2008 Oct 29.
The vertebrate inner ear arises from the otic placode, a transient thickening of ectodermal epithelium adjacent to neural crest domains in the presumptive head. During late gastrulation, cells fated to comprise the inner ear are part of a domain in cranial ectoderm that contain precursors of all sensory placodes, termed the preplacodal region (PPR). The combination of low levels of BMP activity coupled with high levels of FGF signaling are required to establish the PPR through induction of members of the six/eya/dach, iro, and dlx families of transcription factors. The zebrafish dlx3b/4b transcription factors are expressed at the neural plate border where they play partially redundant roles in the specification of the PPR, otic and olfactory placodes. We demonstrate that dlx3b/4b assist in establishing the PPR through the transcriptional regulation of the BMP antagonist cv2. Morpholino-mediated knockdown of Dlx3b/4b results in loss of cv2 expression in the PPR and a transient increase in Bmp4 activity that lasts throughout early somitogenesis. Through the cv2-mediated inhibition of BMP activity, dlx3b/4b create an environment where FGF activity is favorable for PPR and otic marker expression. Our results provide insight into the mechanisms of PPR specification as well as the role of dlx3b/4b function in PPR and otic placode induction.
脊椎动物的内耳起源于耳板,即原头区中与神经嵴区域相邻的外胚层上皮的短暂增厚。在原肠胚形成后期,注定要构成内耳的细胞是颅外胚层中一个区域的一部分,该区域包含所有感觉板的前体,称为前板区域(PPR)。低水平的骨形态发生蛋白(BMP)活性与高水平的成纤维细胞生长因子(FGF)信号传导相结合,通过诱导六/eya/ Dach、iro和dlx转录因子家族的成员来建立PPR。斑马鱼dlx3b/4b转录因子在神经板边界表达,它们在PPR、耳板和嗅板的特化中发挥部分冗余作用。我们证明,dlx3b/4b通过对BMP拮抗剂cv2的转录调控来协助建立PPR。吗啉代介导的Dlx3b/4b敲低导致PPR中cv2表达缺失,以及Bmp4活性在整个早期体节发生过程中持续短暂增加。通过cv2介导的对BMP活性的抑制,dlx3b/4b创造了一个FGF活性有利于PPR和耳标记物表达的环境。我们的结果为PPR特化机制以及dlx3b/4b功能在PPR和耳板诱导中的作用提供了见解。
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